There are three main clinical manifestations of leishmaniasis, which are currently classified as visceral, mucocutaneous, and cutaneous leishmaniasis. The clinical form of leishmaniasis is determined by the Leishmania species, geographical location, and immune response of the host. The leishmaniasis diseases are endemic in 98 countries, frequently with one type being more of a threat over the other two in specific regions. It is estimated that more than 350 million people are at risk, 12 million people are affected worldwide, with 2 million new cases reported per year (1.5 million CL and 0.5 million VL). VL causes 50.000 to 60.000 deaths annually. The leishmaniasis are widely dispersed, with transmission to humans on five continents, but the human disease burden is concentrated mainly in a few major foci. On the other hands Chagas disease, also known as American trypanosomiasis, is a potentially life-threatening illness caused by the protozoan parasite, Trypanosoma cruzi (T. cruzi). It is found mainly in Latin America, where it is mostly transmitted to humans by the faeces of triatomine bugs. An estimated 10 million people are infected worldwide, mostly in Latin America where Chagas disease is endemic. More than 25 million people are at risk of the disease. It is estimated that in 2008 Chagas disease killed more than 10,000 people.
The classification system divides the genus Leishmania into two sub-genera: Leishmania (L) sensu-stricto, present in both Old and New World, and Viannia (V), restricted to the New World. Within these two sub-genera, various species complexes have been individualized (Rioux, 1990). Currently, at least twenty different species are recognized as human infectants. The most prevalent species involved in human cases of leishmaniasis are L. (L) donovani, L. (L) infantum, L. (L) mexicana, L. (L) amazonensis, L. (L) tropica, L. (L) major, L. (L) aethiopica, L. (V) braziliensis, L. (V) guyanensis, L. (V) panamensis and L. (V) peruviana. Each of these species is found in different locations worldwide and is responsible for causing different types of leishmaniasis (Center for Disease Control, 2002).
Visceral leishmaniasis is the most pathogenic of the three types. It is caused by species of L. (L) donovani complex and L. (L) infantum. The common symptoms include irregular fever, weight loss, swelling of the spleen and liver and anemia (World Health Organization, 2010). If left untreated, visceral leishmaniasis will lead to death. Endemic L. (L) infantum visceral leishmaniasis affects mainly children and L. (L) donovani VL affects people of any age group living in urban and rural areas. The onset of this type is usually abrupt, but symptoms may appear 3 weeks to 2 years after exposure.
The clinical features of cutaneous leishmaniasis (CL) tend to vary between and within regions, reflecting different species of parasite or the type of zoonotic cycle concerned, immunological status and also genetically determined response of patients. Two weeks to 2 months after the insect byte, the lesion starts as a papule or nodule at the site of inoculation; its grows slowly, a crust develops centrally, which may fall away, exposing an ulcer with a raised edge and variable surrounding induration which heals gradually over months or years, leaving a depressed scar with altered pigmentation. Satellite nodules at the edge of the lesion are common. Cutaneous leishmaniasis has a wide variety of clinical presentations. WHO estimated in 1500000 the number of new cases yearly in the world. In the Old World CL is caused by 5 species: L infantum, L major, L tropica, L aethiopica and L donovani. In the Americas CL are caused by multiple species of both the Leishmania and Viannia subgenera. The clinical forms included localized, disseminated, diffuse and atypical CL and mucocutaneous leishmaniasis (MCL).
Mucocutaneous leishmaniasis is caused by the metastasis from the skin to the naso-oro pharyngeal mucosal tissues by lymphatic or hematogenous dissemination of L braziliensis, L panamensis and L guyanensis. 
Access to medicines for the treatment of VL, CL and MCL is problematic in the poverty-stricken countries that have the highest burden of cases (WHO 2010). Most research to treat leishmaniasis is focused on the development of improved chemotherapies because current drugs are unsatisfactory (Croft and Yardley, 2002). Pentavalent antimonials, such as meglumine antimoniate and sodium stibogluconate are the most used anti-leishmanial drugs. They are chemically similar and their toxicity and efficacy are related to their antimonial content. While they can be therapeutic, they have unsatisfactory side effects such as nausea, vomiting, anorexia, abdominal pain, myalgia, arthralgia, headache, metallic taste and lethargy. Systemic toxicity (cardiac, renal and hepatic), chemical pancreatitis, decreases in RBCs (Red Blood Cell Count), WBCs (White Blood Cell Count) and platelet counts and reversible peripheral neuropathy (Berman, 1997).
Additionally, these drugs require prolonged treatment (Shyam and Madhukar, 2002; Berman, 2003). The treatment with antimonials includes repeated [daily intramuscular or intravenous] injections for 20-28 days, requiring medical supervision. It is recommended that 20 mg/kg body weight be injected daily over that period of time (Berman, 1997). In addition to these drawbacks, Leishmania parasites are also becoming increasingly resistant to these treatments (Shyam and Madhukar, 2002; Berman, 2003).
Amphotericin B deoxycholate or lipid formulations of amphotericin B is a secondary treatment used for leishmaniasis, especially when antimonial treatment has not been effective (Markle and Makhoul, 2004). This treatment is parenteral in nature and also highly toxic. It was found, however, that a total dose of 15 mg/kg body weight is 100% effective and a dose of 10 mg/kg of liposomal amphotericin B is 97% effective against the Indian visceral disease (Berman, 2003 Sundar 2011). A liposomal formulation reduces the toxicity (Sundar S, 2010), but at a higher cost.
Other currently used drugs include the alkyl-glycero-phosphocholine (miltefosine), Paromomycin, pentamidine isethionate, and ketoconazole. Miltefosine was originally developed as an oral anticancer drug but was shown to have antileishmanial activity. At a dose of 2.5 mg/kg per day for days is recommended by WHO as systemic treatment for Visceral leishmaniasis, post kala-azar dermal leishmaniasis and for New world cutaneous leishmaniasis caused by L mexicana, L panamensis and L guyanensis and for mucocutaneous leishmaniasis in Bolivia. Miltefosine commonly induces gastrointestinal side-effects such as anorexia, nausea, vomiting (38%) and diarrhea (20%). Most episodes are brief and resolve as treatment is continued. Occasionally, the side-effects can be severe and require interruption of treatment. Skin allergy, elevated hepatic transaminase concentrations and, rarely, renal insufficiency may be observed. Miltefosine should be taken after meals, and, if multiple doses are to be taken, they should be divided. Miltefosine is potentially teratogenic and should not be used by pregnant women or women with child-bearing potential for whom adequate contraception cannot be assured for the duration of treatment and for 3 months afterwards (WHO 2010) Paromomycin (aminosidine), an aminoglycoside antibiotic, usually administered intramuscularly, are under study. The 15 mg/kg sulfate is equivalent to 11 mg/kg of base, and the 20 mg/kg sulfate is equivalent to 15 mg/kg of base. Mild pain at the injection site is the commonest adverse event (55%). Reversible ototoxicity occurs in 2% of patients. Renal toxicity is rare. Some patients may develop hepatotoxicity, indicated by raised hepatic enzyme concentrations; tetany has also been reported. (WHO 2010) Paromomycin ointments plus gentamicine or plus methyl benzethonium chloride twice daily for 20 days as shown encouraging results for the treatment of CL. Pentamidine isethionate given intramuscular or by intravenous infusion of 4 mg salt/Kg per day every other day for 3 doses, is recommended for the systemic treatment of CL causes by L panamensis and L guyanensis severe adverse events as diabetes mellitus, severe hypoglycaemia, shock, myocarditis and renal toxicity are recorded. Ketokonazole have variable efficacy in leishmaniasis treatment and is recommended by WHO for L mexicana cutaneous leishmaniasis at a daily adult oral dose of 600 mg for 28 days.
Thermotherapy applications for 30 seconds showed encouraging results as an alternative treatment of CL. The therapy consists in one or two applications of localized heat (50° C.). This therapy has shown as effective as intralesional Sb5+(70% cure rate) in Afghanistan (L. tropica) and more effective (70% cure rate) than systemic Sb5+ in L. major cutaneous leishmaniasis. This device is expensive, and the initial evolution of the disease after thermotherapy is complicated by second-degree burns. Local anaesthesia is necessary.
Cryotheraphie with liquid nitrogen (−195° C.) applied to the lesion once or twice weekly up to 6 weeks also showed encouraging results as an alternative treatment of CL. Liquid nitrogen application requires specific (usually expensive) devices and a skilled health-care provider. Cryotherapy is widely available at dermatology departments but generally not in the field, and the supply chain for liquid nitrogen requires heavy equipment.
Quaternary ammonium compounds such as octadecyltrimethyl ammonium bromide and dodecyltrimethyl ammonium bromide have also been reported to inhibit the growth of L. major promastigotes (Zufferey and Mamoun, 2002). The use of alkyl quaternary ammonium compounds including certain choline analogs for treating or preventing fungal and trypanosomal (e.g., Leishmaniasis) infections is described by Mamoun (2006). The compounds seem to inhibit or perturb choline transport into the parasites, thus inhibiting parasites growth. Common side-effects are anorexia, vomiting, nausea, abdominal pain, malaise, myalgia, arthralgia, headache, metallic taste and lethargy. Electrocardiographic changes depend on the dose and duration of treatment, the commonest being T-wave inversion, a prolonged Q-T interval and arrhythmia. Cardiotoxicity and sudden death are serious but uncommon side-effects. Prolongation of a corrected Q-T interval (>0.5 sec) signals the likely onset of serious and fatal cardiac arrhythmia. Pancreatic enzyme concentrations are commonly raised, but clinical pancreatitis is uncommon. Elevated liver enzyme concentrations, leukopenia, anaemia and thrombopenia are not uncommon.
Other quaternary ammonium salts that are known antibacterials, such as methylbenzethonium chloride, benzethonium chloride, cetalkonium chloride, benzalkonium chloride, and cetrimonium bromide have been used in combination with other drugs such as paromomycin and meglumine antimoniate (Soto et al., 1998; Krause and Kroeger, 1994; Carter et al., 1989; El-On et al., 1985, 1984); as a well as benzethonium chloride, in combination with other drugs such as hexadecyl-phosphorylcholine (Iqbal et al., 2006).
Chagas disease can be treated with either benznidazole or nifurtimox. Both medicines are almost 100% effective in curing the disease if given soon after infection at the onset of the acute phase. However, the efficacy of both diminishes the longer a person has been infected. Benznidazole and nifurtimox should not be taken by pregnant women or by people with kidney or liver failure. Nifurtimox is also contraindicated for people with a background of neurological or psychiatric disorders (World Health Organization, 2010).
Multiple metabolic pathways and specific molecular targets have been studied in trypanosomatid parasites. Membrane lipid biosynthesis pathways are a viable target for anti-trypanosomal compounds since phospholipids have an important role in the cell biology of the parasite and membrane lipid composition differs significantly when compared to mammals.